DESCRIPTION: By 2015, 50% of persons living with HIV (PLWH) in the United States will be 50 years of age or older. In addition, modifiable risk factors (e.g., obesity, hypertension, dyslipidemia, physical inactivity and other unhealthy lifestyle habits) are more pronounced among PLWH due to HIV disease, antiretroviral therapy (ART), and prior or current risky lifestyles. These factors notably increase the risk for adverse cardiovascular events, but may also promote more rapid decline in cognitive function at significantly younger ages than non- HIV infected persons. Consequently, PLWH age 50 and over represent a highly vulnerable group who are likely to shoulder a disproportionately higher disease burden with multimorbidities. Immune activation is an underlying mechanism shared by the aging process, HIV, and ART treatment that hastens immune senescence and induces a chronic inflammatory state that is associated with greater risk for cardiovascular disease (CVD) and cognitive impairment (CI). Carotid artery intima media thickness [c-IMT]) for example, a marker of endothelial vascular function, has been consistently associated with T cell activation and other inflammatory markers associated with cognitive impairment in persons with and without HIV; c-IMT changes however, occur up to 20 years younger and at a more accelerated pace in PLWH. Strategies that reduce CVD and CI risk factors and mitigate the chronic inflammatory state associated with aging and HIV is essential for greater longevity and improved quality of life in this population. Aerobic exercise lowers CVD risk indicators, including inflammatory biomarkers in older adults, and is established to improve physical, psychological, and cognitive function with aging, but has limited testing in PLWH. Animal research has provided the most robust evidence that aerobic exercise stimulates neuronal growth and synaptodendritic complexities involved in learning and memory with increasing levels of brain derived neurotrophic factor (BDNF) possibly playing a crucial role in this process. Regular aerobic exercise performed 5 times per week for 150 minutes has also been shown to improve aspects of neurocognitive function in community-dwelling older adults. Only one exercise study however, has examined the effect of exercise on cognition in PLWH and was limited by a self- reported, unreliable indicator of cognitive status. No studies have reported whether exercise improves cognition in this population using objective assessments or examined the potential mechanisms involved. Our home- based aerobic exercise intervention, the 'Let's Move Program' has been tested and is effective for lowering CVD risk in previous trials of older caregivers and adults with advanced CVD. The proposed efficacy trial will test the Lets Move Program among 160 PLWH randomized to either the Let's Move intervention (N=80) or an attention control condition, Let's Flex (N=80), and followed for 18-months. Participants will be > 50 years of age, sedentary, demonstrate objectively measured CI, and have at least two CVD risk factors. Motivational Interviewing (MI) will be used to promote exercise self-efficacy and optimize adherence to the intervention.